甲氨蝶呤插层MgAl-LDH复合物的制备与释药性能  

Preparation and Release Properties of Methotrexate Intercalated MgAl-LDH Composites

作　　者：梁良 任锦 徐常青 代军[1] 李东霖[1] LIANG Liang;REN Jin;XU Chang-qing;DAI Jun;LI Dong-lin(Analytical and Testing Center,Jiujiang University,Jiujiang332005,Jiangxi,China;School of Pharmacy andLife Sciences,Jiujiang University,Jiujiang 332005,Jiangxi,China)

机构地区：[1]九江学院分析测试中心,江西九江332005 [2]九江学院药学与生命科学学院,江西九江332005

出　　处：《精细化工》2019年第6期1166-1172,共7页Fine Chemicals

基　　金：国家自然科学基金项目(81860631);江西省卫健委科研项目(20195633)~~

摘　　要：以Mg(NO3)2·6H2O和Al(NO3)3·9H2O为主要原料,采用共沉淀联合水热合成法制备了甲氨蝶呤插层镁铝层状双氢氧化物复合物(MTX-LDH),通过正交实验分析了主要工艺条件对MTX-LDH复合物载药率、粒径及其分散性的影响。结果表明:当反应温度为60℃、Mg(NO3)2·6H2O和Al(NO3)3·9H2O的投入量分别为2.67和1.33 mmol、MTX和聚乙二醇400加入量分别为0.20 mmol和15 mL时,复合产物单分散性良好,粒径均值为175.6 nm,载药率达18.90%。利用FTIR、XRD、TG以及TEM对样品结构、热力学性质和微观形貌进行了测定。重点考察了MTX-LDH复合物在不同pH缓冲溶液中的释药性能,表明其具备pH响应型释放特性,在pH=5.8的弱酸环境中缓释效果良好,12h累积释药率为93.7%,并通过热力学释药模型确定其缓释机理为层板溶蚀与置换扩散并存的缓释机制。Methotrexate intercalated Mg-Al layered double hydroxide composites(MTX-LDH) were prepared via combination of coprecipitation and hydrothermal synthesis by using Mg(NO3)2·6 H2O and Al(NO3)3·9 H2O as main materials. The effects of main technological conditions on the drug loading rate,particle size and particle size dispersion of MTX-LDH were analyzed by orthogonal experiments. The results showed that the composites had good monodispersity with an average particle size of 175.6 nm, and exhibited high drug loading rate of 18.90% when the reaction temperature was 60 ℃, and the amount of Mg(NO3)2·6 H2O, Al(NO3)3·9 H2O, MTX and polyethylene glycol 400 were 2.67 mmol, 1.33 mmol, 0.20 mmol and 15 mL, respectively. The structure, thermodynamic properties and micro-morphology of the samples were studied by FTIR, XRD, TG and TEM. The release properties of MTX-LDH particles in different pH buffer solutions were investigated. The results indicated that the composites had pH-responsive release characteristics and good sustained release properties in weak acid environment(pH=5.8), and the cumulative release rate at 12 h was up to 93.7%. Moreover, the release mechanism of laminate dissolution coexisting with displacement diffusion was confirmed by the thermodynamic release model.

关 键 词：层状双氢氧化物 甲氨蝶呤 粒径 载药率 缓释性能 医药原料 

分 类 号：O614[理学—无机化学] TB33[理学—化学]